CAR-T cell signalling
CAR-T cell signalling. A chimeric antigen receptor fuses an antibody scFv (here anti-CD19) to a hinge, transmembrane domain, one or more costimulatory domains (CD28 and/or 4-1BB) and the CD3ζ activation module. Antigen engagement fires Signal 1 (CD3ζ → LCK → ZAP-70 → LAT/SLP-76 → NFAT, NF-κB, AP-1) and Signal 2 (CD28 → PI3K/AKT; 4-1BB → TRAF → NF-κB), driving proliferation, cytotoxicity and cytokines — opposed by exhaustion checkpoints. Click any protein for the matching Assay Genie In Vivo antibody or ELISA kit.
The receptor. A CAR is a single synthetic protein: an antibody-derived scFv that recognises a surface antigen (classically CD19 on B-cell malignancies), a hinge and transmembrane domain, then intracellular costimulatory and CD3ζ modules. Generations differ only in the tail — 1st: CD3ζ alone; 2nd: CD3ζ + one costimulator (CD28 or 4-1BB); 3rd: CD3ζ + both.
Signal 1 & 2. Antigen binding clusters the CAR; CD3ζ ITAMs are phosphorylated by LCK, recruiting ZAP-70 and building the LAT/SLP-76 signalosome and PLCγ1. This splits into the Ca2+/calcineurin/NFAT, PKCθ/CBM/NF-κB and Ras/MAPK/AP-1 arms. Costimulation adds durability: CD28 → PI3K → AKT → mTOR (rapid, effector-like) and 4-1BB → TRAF2 → NF-κB (slower, memory/persistence).
Output & exhaustion. The transcription factors drive IL-2 and proliferation, IFN-γ, cytotoxic granules (perforin, granzyme B) and FasL to kill the target — while excess IL-6 / TNF underlie cytokine-release syndrome. Chronic antigen drives exhaustion: PD-1, TIM-3, LAG-3 recruit SHP-2 to dephosphorylate the cascade. Assay Genie In Vivo antibodies cover the surface layer (anti-CD19, anti-CD28, anti-4-1BB, anti-PD-1/TIM-3/LAG-3) and the cytokines; the intracellular machinery is covered by ELISA kits. For research use only; not for diagnostic or therapeutic procedures. Mouse targets shown where available.
Every protein node links to a product: In Vivo antibodies for the CAR target, costimulators, checkpoints and cytokines; the intracellular kinases, adaptors and transcription factors open the matching ELISA kit.